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At least 1,099 records · Page 61Linked to original sources
PubMed2002

Antischistosomal bioactivity of isoflavonoids from Millettia thonningii (Leguminosae).

Extracts of the seeds of the leguminous tree Millettia thonningii are molluscicidal and schistosomicidal and contain a mixture of isoflavonoids and 3-phenylcoumarins. Robustic acid and a pure mixture of alpinumisoflavone and dimethylalpinumisoflavone, as characterized by nuclear magnetic resonance, were isolated from a dichloromethane extract. The bioactivity of these compounds against Schistosoma mansoni miracidia, cercariae, and adult worms was tested in vitro. Both robustic acid and the alpinumisoflavone mixture killed cercariae and adult schistosomes in vitro. At sublethal concentrations of the isoflavonoids, reductions in miracidial motility were measured using a video-imaging technique. The inhibition of mitochondrial electron transport at site I by the isolated isoflavonoids was also investigated. The results suggest that robustic acid and at least 1 alpinumisoflavone compound from the dichloromethane extract of the seeds of M. thonniogii are responsible for some of the observed bioactivity of this extract against schistosomes.

Animals↗
PubMed2004

A 3D similarity method for scaffold hopping from known drugs or natural ligands to new chemotypes.

A primary goal of 3D similarity searching is to find compounds with similar bioactivity to a reference ligand but with different chemotypes, i.e., "scaffold hopping". However, an adequate description of chemical structures in 3D conformational space is difficult due to the high-dimensionality of the problem. We present an automated method that simplifies flexible 3D chemical descriptions in which clustering techniques traditionally used in data mining are exploited to create "fuzzy" molecular representations called FEPOPS (feature point pharmacophores). The representations can be used for flexible 3D similarity searching given one or more active compounds without a priori knowledge of bioactive conformations or pharmacophores. We demonstrate that similarity searching with FEPOPS significantly enriches for actives taken from in-house high-throughput screening datasets and from MDDR activity classes COX-2, 5-HT3A, and HIV-RT, while also scaffold or ring-system hopping to new chemical frameworks. Further, inhibitors of target proteins (dopamine 2 and retinoic acid receptor) are recalled by FEPOPS by scaffold hopping from their associated endogenous ligands (dopamine and retinoic acid). Importantly, the method excels in comparison to commonly used 2D similarity methods (DAYLIGHT, MACCS, Pipeline Pilot fingerprints) and a commercial 3D method (Pharmacophore Distance Triplets) at finding novel scaffold classes given a single query molecule.

Cyclooxygenase 2↗
PubMed2004

Tailoring modification of deoxysugars during biosynthesis of the antitumour drug chromomycin A by Streptomyces griseus ssp. griseus.

Chromomycin A3 is a member of the aureolic acid group family of antitumour drugs. Three tailoring modification steps occur during its biosynthesis affecting the sugar moieties: two O-acetylations and one O-methylation. The 4-O-methylation in the 4-O-methyl-D-oliose moiety of the disaccharide chain is catalysed by the cmmMIII gene product. Inactivation of this gene generated a chromomycin-non-producing mutant that accumulated three unmethylated derivatives containing all sugars but differing in the acylation pattern. Two of these compounds were shown to be substrates of the methyltransferase as determined by their bioconversion into chromomycin A2 and A3 after feeding these compounds to a Streptomyces albus strain expressing the cmmMIII gene. The same single membrane-bound enzyme, encoded by the cmmA gene, is responsible for both acetyl transfer reactions, which convert a relatively inactive compound into the bioactive chromomycin A3. Insertional inactivation of this gene resulted in a mutant accumulating a dideacetylated chromomycin A3 derivative. This compound, lacking both acetyl groups, was converted in a two-step reaction via the 4E-monoacetylated intermediate into chromomycin A3 when fed to cultures of S. albus expressing the cmmA gene. This acetylation step would occur as the last step in chromomycin biosynthesis, being a very important event for self-protection of the producing organism. It would convert a molecule with low biological activity into an active one, in a reaction catalysed by an enzyme that is predicted to be located in the cell membrane.

Acetylation↗
PubMed2005

Synthesis and insecticidal evaluation of propesticides of benzoylphenylureas.

Two series of benzoylphenylurea derivatives were synthesized as candidate propesticides by a nucleophilic addition reaction between 2,6-difluronbenzoyl isocyanate and N-substitutedaniline. The new compounds were identified by 1H NMR spectroscopy, electron ionization-mass spectrometry, and elemental analyses. The bioactivities of the new compounds were evaluated. All of the propesticides reported here were soluble in most organic solvents, and their hydrophobicities were improved obviously. The result of the bioactivities of the new compounds against Oriental armyworm showed that some of the new compounds are good as compared to diflubenzuron and penfluron.

Aniline Compounds↗
PubMed2006

A quantitative structure-activity relationship study of herbicidal analogues of alpha-hydroxy-substituted 3-benzylidenepyrrolidene-2,4-diones.

A series of pyrrolidine-2,4-dione and piperidine-2,4-dione derivatives were prepared and evaluated for their herbicidal activities where some of these compounds exhibited good bioactivity against Echinochloa crus-galli in comparison with sulcotrione. Quantitative structure-activity relationship studies were performed on these compounds using physicochemical parameters (hydrophobic, electronic, and Taft) as independent parameters and herbicidal activity as a dependent parameter, where herbicidal activity correlated best (r > 0.8) with hydrophobic (pi(o) + pi(p)), steric (Es), STERIMOL (B4), indicator (H(M)), van der Waals volume (V), and electronic parameter (sigma(m) + sigma(p)) in this set of molecules; the optimum van der Waals volume for R(2) is about 41.8 A3; when B4 is equal to 3, the target molecule possessed the lowest herbicidal activity.

Benzylidene Compounds↗
PubMed2000

Formation of novel D-ring and E-ring isoprostane-like compounds (D4/E4-neuroprostanes) in vivo from docosahexaenoic acid.

Free radical-mediated oxidant injury and lipid peroxidation have been implicated in a number of neural disorders. We have reported that bioactive prostaglandin D2/E2-like compounds, termed D2/E2-isoprostanes, are produced in vivo by the free radical-catalyzed peroxidation of arachidonic acid. Docosahexaenoic acid, in contrast to arachidonic acid, is the most abundant unsaturated fatty acid in brain. We therefore questioned whether D/E-isoprostane-like compounds (D4/E4-neuroprostanes) are formed from the oxidation of docosahexaenoic acid. Levels of putative D4/E4-neuroprostanes increased 380-fold after oxidation of docosahexaenoic acid in vitro from 15.2 +/- 6.3 to 5773 +/- 1024 ng/mg of docosahexaenoic acid. Subsequently, chemical approaches and liquid chromatography electrospray ionization tandem mass spectrometry definitively identified these compounds as D4/E4-neuroprostanes. We then explored the formation of D4/E4-neuroprostanes from a biological source, rat brain synaptosomes. Basal levels of D4/E4-neuroprostanes were 3.8 +/- 0.6 ng/mg of protein and increased 54-fold after oxidation (n = 4). We also detected these compounds in fresh brain tissue from rats at levels of 12.1 +/- 2.4 ng/g of brain tissue (n = 3) and in human brain tissue at levels of 9.2 +/- 4.1 ng/g of brain tissue (n = 4). Thus, these studies have identified novel D/E-ring isoprostane-like compounds that are derived from docosahexaenoic acid and that are formed in brain in vivo. The fact that they are readily detectable suggests that ongoing oxidative stress is present in the central nervous system of humans and animals. Further, identification of these compounds provides a rationale for examining their role in neurological disorders associated with oxidant stress.

Animals↗
PubMed2006

Biocontrol efficacy of Cestrum diurnum L. (Solanaceae: Solanales) against the larval forms of Anopheles stephensi.

Cestrum diurnum L. (Solanaceae: Solanales) is a multistemmed shrub that is also known as 'Day Jasmine'. The efficacy of the plant as a strong biocontrol agent of the larval anopheline mosquito was evaluated in the laboratory and bioactive ingredients were characterized by thin layer chromatography (TLC) and infrared (IR) analysis. Thin layer chromatographic analysis revealed the presence of steroidal compound as a bioactive ingredient and IR analysis reported the presence of O-H group, C-S bond as a -CH2S group, H bonded -C=O group and carbonyl stress of esters. The LC50 value of the active ingredient was determined as 0.70, 0.89, 0.90 and 1.03 mg/100 mL-1, for 1st, 2nd, 3rd and 4th instar larva respectively in 24 h study period. The active component was analyzed by GLC and GLC-MS and altogether 14 components were detected.

Animals↗
PubMedDate not supplied

[Interaction of proteins with platinum and palladium compounds with differing biological activities].

Protein interaction with bioactive platinum and palladium complex compounds was studied by solid-phase sorbent assay (SSA), turbidimetry, isoelectric focusing and circular dichroism. In SSA reaction ability of metal compounds can be represented as follows: [equation: see text] Reaction ability of proteins can be represented as follows: hemoglobin > serum albumin > immunoglobulin. The reaction products of serum albumin and metal compounds demonstrated more alkaline isoelectric points then the intact albumin resulting from adding positively charged metal centers [MeCl+, Me2+, [Me(H2O)n]2+, [Me(H2O)nCl]+ to albumin molecules. In metal-protein complexes circular dichroism demonstrated the diminution of alpha-helix structure percentage if compared with intact albumin, the most prominent effect being caused by K2[PdCl]4. The conformational distortion of albumin was significant. Metal compounds mostly affected the optical activity of S-S-protein bands (251-254 nm). Experimental evidence confirmed the hypothesis that platinum metal complexes with high reaction ability are less toxic than those with low reaction ability.

Animals↗
PubMed2004

Bioactive lignans from a cultivar of Helianthus annuus.

A bioassay-guided fractionation of water extracts from Helianthus annuus cv. SH-222 was carried out. Ten lignans and a phenylpropanoid were isolated from the polar bioactive fractions of H. annuus. This study is the first to report lignans as constituents of sunflower and is the first time that tanegool has been isolated as a natural aglycone. Additionally, we report biological activities of the isolated compounds. The general bioactivity has been evaluated using the wheat coleoptiles bioassay. The phytotoxic activities of compounds pinoresinol, lariciresinol, dihydro-dehydrodiconiferilic alcohol, and l-(4'-hydroxy-3'-methoxyphenyl)-2-[4' '-(3hydroxypropyl)-2' '-methoxyphenoxy]propane-l,3-diol were also evaluated in a bioassay on the standard target species. The structure-activity relationships are discussed.

Chemical Fractionation↗
PubMed2006

Establishment and application of a high throughput model for Rho kinase inhibitors screening based on fluorescence polarization.

Rho kinase (ROCK) inhibitors are effective candidates for neural or cardiovascular disorders. High throughput model for screening ROCK inhibitors is a basic foundation to pick up ROCK inhibitors from thousands of compounds for drug developing. The high throughput model was established based on purified recombinant rat ROCK catalytic domain (rROCK-CD) from Escherichia coli (E. coli). There are two steps of reaction in the model: incubation of 5.0 microl recombinant rROCK-CD (2.0 microg/ml), 5.0 microl different compounds, 5.0 microl fluorescent S6-peptide (200 nM), and 5.0 microl ATP (10 microM) at 37 degrees C for 60 min was made the first reaction, and the second reaction was made by incubating them with additional 60 microl binding reagent at ambient temperature for 30 min. The phosphorylated S6 peptide can bind to a binding reagent, and the fluorescence varies from low polarization to high according to the amount of the phosphorylated peptide. IC50 was calculated based on polarization variation. Compound, which IC50 was less than 10 microM, was recognized as a lead compound which taken bioactivity evaluation in PC12 by observing neurite outgrowth. The Z'-factor of the model is 0.81 (above 0.5). The model screened five lead compounds from 3294, which promoted neurite outgrowth to different extent. The results suggested that the model is suitable for high throughput screening (HTS), and the five lead compounds are worth of further investigation.

Animals↗
PubMedDate not supplied

Limonoids from the endemic Brazilian species Raulinoa echinata.

Phytochemical survey of stems and leaves of the South Brazilian endemic Raulinoa echinata Cowan, Rutaceae led to the isolation of five limonoid derivatives: the widespread limonin, limonexic acid, kihadalactone B, a methoxylated limonexic acid derivative and a degraded limonoid structurally related to fraxinellone. The two latter compounds have been isolated for the first time. These compounds displayed weak inhibitory activity when assayed in vitro against trypomastigote forms of Trypanosoma cruzi. In this paper, the isolation, structure elucidation and bioactivity of these compounds are reported.

Animals↗
PubMed2026

QTLs associated with phenolic acid accumulation and antioxidant activity in tropical maize.

Maize represents a significant source of phytochemicals, with phenolic acids standing out as one of the most extensively studied functional compound families. These bioactive molecules have gained attention for their potent antioxidant properties and potential contributions to human health improvement. To evaluate the segregation of phenolic compounds in maize and its genetic basis, this study was conducted to identify quantitative trait loci (QTLs) associated with major phenolic compounds and their antioxidant capacity. The mapping population comprised 100 recombinant inbred lines (RILs) derived from the cross between P84 and Kilima. Twelve traits were analyzed: free and cell wall-bound antioxidant capacity, total phenolic content, and contents of p-coumaric acid, ferulic acid, three isomers of di-ferulic acid, and three isomers of tri-ferulic acid. The RILs exhibited substantial diversity in phenolic compound profiles. In total, 19 QTLs were identified for nine traits, with the number of associated regions ranging from 1 to 5 and explaining between 2.95% and 37.48% of the phenotypic variation. This research provides substantial evidence for the co-localization of major QTLs for principal phenolic acids in maize with genomic regions harboring genes putatively related to their biosynthesis and biotic resistance. This is the first study to report QTLs associated with triferulic acids in maize. The identified regions co-localizing with biotic stress resistance genes represent targets for marker-assisted selection toward the improvement of phenolic acid accumulation in maize breeding programs.

QTLs↗
PubMed1996

Chlorinated annonaceous acetogenins and their bioactivities.

4(S)-Chloro-4-deoxygigantetrocin A and 4(S), 18-dichloro-4,18-dideoxyasimilobin were obtained by treating gigantetrocin A with triphenylphosphine and CCl4. The structures were determined by spectroscopic methods. The chlorinated compounds show decreased bioactivities in the brine shrimp lethality test and against human tumor cell lines.

4-Butyrolactone↗
PubMed2005

The patellazoles inhibit protein synthesis at nanomolar concentrations in human colon tumor cells.

The patellazoles are a family of compounds consisting of a 24-member macrolide ring with a thiazole-epoxide tail. The opening of this epoxide does not greatly affect the bioactivity of these compounds, although the cellular toxicity is generally decreased. The patellazoles are extremely cytotoxic towards HCT 116 human colon tumor cells. Treatment with nanomolar amounts of these compounds results in immediate inhibition of protein synthesis and cell cycle arrest at the G1 and S phase. HCT 116 wild-type cells underwent apoptosis after extended patellazole treatment. Although treatment with the patellazoles resulted in an increased amount of p53, the p53 null cells were still strongly affected by treatment. The inhibition of translation by patellazole treatment is linked to the inhibition of the mTOR/p70 pathway. Like the mTOR inhibitor rapamycin, the patellazoles inhibit translation through the 4EBP1 and S6 kinase pathways. However, the cytotoxicity of rapamycin and the patellazoles differs greatly in HCT 116 cells. The cellular target of the patellazoles is still unknown; the patellazole-induced inhibition of this pathway occurs either downstream or parallel to AKT.

Animals↗
PubMed1999

Heterocyclic HIV-1 protease inhibitors.

[formula: see text] A series of simple heterocyclic HIV-1 protease inhibitors were developed on the basis of size, shape, and electronic complementarity to the active site of the enzyme. The C2-symmetric heterocycles do not contain a transition-state isostere nor are they active site directed irreversible inhibitors; thus, they represent the success of a new design strategy. The first generation heterocycles inhibit the protease in the micromolar range, whereas control compounds show no bioactivity at the same concentrations.

Crystallography, X-Ray↗
PubMed2000

Synthesis and bioactivity of 6alpha- and 6beta-hydroxy analogues of castasterone.

The reduction of castasterone with sodium in ethanol produced chiefly the known 6alpha-hydroxy stereoisomer, whereas reduction with sodium orohydride in methanol afforded mainly the novel 6beta-epimer. Both compounds showed variable bioactivity through four separate assays via the rice leaf lamina inclination bioassay. However, when treated with an appropriate statistical program to remove outliers, the averaged results clearly indicated that the two 6-hydroxy epimers possess comparable and significant bioactivity, which is, however, lower than that of castasterone or brassinolide. When applied together with 1000 ng of the auxin, indole-3-acetic acid (IAA), the activity of both the 6alpha and 6beta hydroxy epimers was enhanced by ca. one order of magnitude across a wide range of doses.

Cholestanols↗
PubMed2006

Scaffold hopping through virtual screening using 2D and 3D similarity descriptors: ranking, voting, and consensus scoring.

The ability to find novel bioactive scaffolds in compound similarity-based virtual screening experiments has been studied comparing Tanimoto-based, ranking-based, voting, and consensus scoring protocols. Ligand sets for seven well-known drug targets (CDK2, COX2, estrogen receptor, neuraminidase, HIV-1 protease, p38 MAP kinase, thrombin) have been assembled such that each ligand represents its own unique chemotype, thus ensuring that each similarity recognition event between ligands constitutes a scaffold hopping event. In a series of virtual screening studies involving 9969 MDDR compounds as negative controls it has been found that atom pair descriptors and 3D pharmacophore fingerprints combined with ranking, voting, and consensus scoring strategies perform well in finding novel bioactive scaffolds. In addition, often superior performance has been observed for similarity-based virtual screening compared to structure-based methods. This finding suggests that information about a target obtained from known bioactive ligands is as valuable as knowledge of the target structures for identifying novel bioactive scaffolds through virtual screening.

Cyclin-Dependent Kinase 2↗